Role of tumor necrosis factor-alpha in disease states and inflammation.

To review the animal and human data defining the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome, the systemic inflammatory response syndrome, and related pathologic states. The international English language literature from 1975 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies. Those animal and human studies that focused on the mechanisms of action of TNF, its role in the inflammatory cytokine network, and the potential uses of anti-TNF therapies were emphasized. Animal studies were selected based on the relevance of the model to the pathogenesis of the human systemic inflammatory response syndrome. Where they provided supportive evidence, human studies were selected on the basis of study design. TNF plays a major role in systemic inflammatory response syndrome secondary to infection, burns, trauma or hemorrhagic shock, and pancreatitis. TNF influences the outcome of other infectious processes, including allograft rejection, ischemia-reperfusion injury, delayed-type hypersensitivity, and granuloma development. The administration of anti-TNF antibodies, soluble TNF receptors, and related fusion proteins may limit organ damage and decrease mortality rate. Although the regulated release of TNF may exert normal physiologic effects, the uncontrolled production of TNF may lead to organ dysfunction and death. TNF mediates a variety of other physiologic processes that are unrelated to sepsis syndrome. New anti-TNF therapies appear to attenuate the injurious actions of TNF.